Electroacupuncture Stimulation Alleviates Inflammatory Pain in Male Rats by Suppressing Oxidative Stress.

In the present study, we focused on whether the analgesic effect of Electroacupuncture (EA) is related to the regulation of oxidative stress. We established a chronic inflammatory pain model in male rats by a single injection of complete Freund's adjuvant (CFA) and then treated the animals with daily EA stimulation at the site of "zusanli". The analgesic effect of EA was evaluated by measuring the paw withdrawal threshold (PWT) when rats received mechanical and thermal pain stimulation. The levels of inflammation-related molecules and oxidative stress-related markers in the spinal cord were measured by western blotting or ELISA kits. EA stimulation and antioxidants effectively increased the PWT in CFA rats. Co-treatment of CFA rats with the ROS donor t-butyl hydroperoxide (t-BOOH) further decreased the PWT and weakened the analgesic effect of EA. EA treatment inhibited inflammation and oxidative stress, as shown by decreased levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, and MDA and increased activity of SOD and catalase. Moreover, EA reduced the expression of p-p38, p-ERK, and p-p65 and simultaneously downregulated the expression of TRPV1 and TRPV4 in CFA rats. In an in vitro study, direct stimulation with t-BOOH to the C6 cells increased the production of TNF-alpha, IL-1beta, IL-6, activated p38, ERK, and p65 and up-regulated the expression of TRPV1 and TRPV4, and these effects could be prevented by the ROS scavenger PBN. Taken together, our data indicate that the inhibition of oxidative stress and the generation of ROS contribute to the analgesic effect of EA in male CFA rats.

Plasma Steroids and Endocannabinoids Used as Biomarkers to Assess the Pruritus Severity of Patients With Prurigo Nodularis.

BACKGROUND: Prurigo nodularis (PN) as an extremely pruritic and hyperplastic chronic dermatosis induces psychologically and physiologically stressful responses. PN-induced responses in the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG) axes and endocannabinoid system (ECS) are abnormal. Extant studies on the PN's pathogenesis mostly focused on the PN's psychological responses. To date, the PN's physiological responses remain not been fully uncovered yet. OBJECTIVES: To investigate the PN-induced physiological responses via the levels of five steroids and two endocannabinoids combined with their ratios in plasma and examine the association between the psychological and physiological responses. MATERIALS AND METHODS: Thirty-six patients with PN, 36 age- and gender-matched healthy controls were recruited. The PN's psychological symptoms including pruritus severity, pain and life quality were measured with the visual analog scale, the prurigo score index, numerical rating scale, verbal rating scale and dermatology life quality index. Their concentrations of steroids and endocannabinoids were determined with liquid chromatography-tandem mass spectrometry. RESULTS: Compared to controls, the PN patients showed lower plasma levels in cortisol, cortisone, N-arachidonoyl-ethanolamine (AEA), and the ratio of DHEA to 1-arachydonoyl glycerol (1-AG), which negatively moderately and over correlated with PN's symptoms, especially with the pruritus severity. Additionally, the PN patients exhibited higher levels in the ratios of testosterone and 1-AG to cortisol, which positively moderately and over correlated with pruritus severity. Thus, the seven biomarkers would be sensitive and reliable biomarkers for assessing the pruritus severity of PN because they met the screening criteria that the biomarkers show intergroup differences and showed moderate or over correlation with the pruritus severity of PN. CONCLUSIONS: To the best of our knowledge, this is the first study exploring PN-induced physiological responses. The findings suggest that alterations in these three endocrine systems may lead to new insights to psychological mechanisms and responses to prurigo nodularis.

Estimates of the effects of physical activity on osteoporosis using multivariable Mendelian randomization analysis.

This study estimates causality of physical activity (PA) on bone mineral density (BMD) by conducting multivariable Mendelian randomization (MR). The findings suggest that habitual vigorous PA increases lumbar spine BMD, and higher overall acceleration average would improve forearm BMD. The results could promote PA intervention targeting individuals with optimized type. INTRODUCTION: Evidence from epidemiologic studies showed type, frequency, and duration of PA influenced BMD. However, these observational studies may be confounded by many factors, resulting in spurious associations. We aimed to conduct multivariable MR to estimate the causal effect of self-reported and device-measured PA on osteoporosis. METHODS: Three self-reported and two device-measured PA-related traits were selected as exposures. Outcomes were BMD at different skeletal sites: femoral neck BMD (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD). Exposure datasets were obtained from UK Biobank with total 377,234 subjects. Outcome datasets were obtained from GEFOS consortium with 53,236 subjects. Standard MR analysis and multivariable MR were conducted to assess the total and direct causal effect of PA on BMD. RESULTS: For self-reported PA, inverse-normalized moderate-to-vigorous had a direct causal effect on FN BMD independently (ß = - 1.116 (95% confidence interval, 95%CI: - 2.210, - 0.023), P = 0.045); vigorous PA showed a direct effect (ß = 3.592 (95%CI: 0.310, 6.874), P = 0.032) on LS BMD independently. While overall acceleration average and fraction of accelerations both had a direct causal effect on FA BMD independently. CONCLUSIONS: Habitual vigorous PA could increase LS BMD. Individuals with higher overall acceleration average would have a higher FA BMD.

[Color stability of computer aided design and computer aided manufacture composite ceramic/resin cements after accelerated ageing].

Objective: To investigate the color stability of computer aided design and computer aided manufacture (CAD/CAM) composite ceramic/resin cements after accelerated ageing. Methods: Twelve groups (ten samples each group) were used as experimental groups, which were composed of CAD/CAM composite ceramic of three kinds of thickness (0.50, 0.75, 1.00 mm) (Lava Ultimate) associated with resin cements (Variolink N) of four colors (A1, A3, T, BL1). Another three groups of CAD/CAM composite ceramic/resin cements of three different kinds of thickness (0.50, 0.75, 1.00 mm) were used as control groups (ten samples each group). All samples were put into the xenon lamp ageing instrument to implement accelerated ageing. Spectrophotometers were used to measure the lightness (L(*)), red green color value (a(*)) and blue yellow color value (b(*)) of all samples before and after accelerated ageing process, and the changes of color variation (ΔE) was calculated. The effect of composite ceramic thickness and resin cement color on the changes of color variation (ΔE) before and after the ageing of CAD/CAM composite ceramic/resin cement and whether there was an interaction between them were tested by two-way ANOVA. Results: Before and after accelerated ageing, the ΔE of CAD/CAM composite ceramic/resin cements were <3.3. Two-way ANOVA showed that the thickness of CAD/CAM composite ceramics had an effect on ΔE (F=27.025, P<0.001), and the color of resin cement also had an effect on ΔE (F=15.606, P<0.001), but there was no interaction between them (F=0.534, P=0.829). Conclusions: The thickness of CAD/CAM composite ceramics and the color of resin cements could both affect the color stability of composite ceramic/resin cements combination. However, the resulted color change is within the clinically acceptable range.

[Effects of thermal cycling on mechanical properties of resin-ceramic composites].

Objective: To investigate the influence of thermal cycling on the mechanical properties of resin-ceramic composites. Methods: The different groups of resin-ceramic composites A (Lava Ultimate, 3M ESPE, USA), B (block HC, Shofu, Japan), C (Hyramic, Upcera, China), D (Vita Enamic, Vita, German), and the feldspar ceramic E (Mark Ⅱ, Vita, German) were included in this study. The properties of these groups (with 30 samples in each group), including flexural strength, flexural modulus and Vickers hardness were tested before and after thermal cycling (0, 10 000 and 20 000 cycles, respectively). The data were statistically analyzed. Results: Before thermal cycling, the flexural strength of groups A, B and C [(166.28±13.78) MPa, (170.21±11.36) MPa and (202.04±16.55) MPa] were higher than those of groups D and E [(137.09±8.83) MPa and (119.35±5.98) MPa], and the flexural modulus [(62.39±3.40) GPa] and Vickers hardness [(406.97±14.73) HV] of E group were higher than those of other groups (P<0.05). The flexural strength, flexural modulus and Vickers hardness of groups D and E did not change after thermal cycling (all P>0.05), while those of groups A, B and C decreased (all P<0.05). Conclusion: After thermal cycling, the mechanical properties of the A, B and C groups decreased, while those of the groups D and E were stable.

[Copy number variants analysis in whole-genome of patients with lipoma tethered cord syndrome].

Objective: To explore the abnormality of chromosomes of patients with lipoma tethered cord syndrome and the probable association between Copy Number Variations (CNV) and lipoma tethered cord syndrome. Methods: By using the Agilent SurePrint G3 Human CGH 8×60K Microarray Kit, we performed genome-wide screening for CNV on 11 patients with lipoma tethered cord syndrome adopted by the Neurosurgery Department of Chinese PLA General Hospital and their healthy parents from March 2015 to May 2015. We analyze CNVs got by the kit against the gene databases. Unrelated confirmed polymorphisms contained in Database of Genomic Variants (DGV) were discarded. Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER) helps us with similarity inquiry, and UCSC Genome Browser helps in identification of non-polymorphic CNV. Biological process, cellular component and molecular function enrichment of these genes were conducted to confirm the association between the CNV and lipoma tethered cord syndrome. Results: 17 CNV were discovered by aCGH in 11 patients. Chr8: 39258894-39386158 and Chr15: 20481702-22509254 showed a high frequency of 5/11. Angelman syndrome and Prader-Wolli syndrome were found to be associated with the CNV of Chr15. Gene function enrichment analysis revealed that ADAM5P and ADAM3A contained in CNV obtained from patients with lipoma tethered cord syndrome was also associated with orofacial clefts. Conclusions: CNV in Chr8 and Chr15 of patients with lipoma tethered cord syndrome had a higher frequency than that of common human. It revealed that there is probable association between these two pieces of CNV and lipoma tethered cord syndrome. To explorer related genes or CNV, focusing on certain type of NTDs may increase the research efficiency and get more accurate results.

The effect of leflunomide on the transplanted endometriosis lesions in SD rats.

OBJECTIVE: To investigate the effects of the leflunomide (LEF) on the size of the transplanted endometriosis (EMS) lesions and trans- forming growth factor (TGF) -ß1gray level in SD rats. MATERIALS AND METHODS: EMS was surgically induced in rats by autologous trans- plantation and the focal volume was also measured. The rats were divided into three groups: group A: normal SD rats, group B: rats irrigated by one ml-kg⁻¹d⁻¹ saline for three weeks, and group C: rats irrigated by 35 mg-kg⁻¹d⁻¹ LEF for three weeks. The rats were then sacrificed and measured their focal volume and TGF-ß1 gray value with immunohistochemical method. RESULTS: The sizes of the focal volume in group C were significantly reduced compared to the rats before feeding, and the volume in group C was smaller than group B after feeding and so was the TGF-ß1. CONCLUSION: LEF could be a new therapeutic drug for EMS.

Molecular cloning and analysis of a receptor-like promoter of Gbvdr3 gene in sea island cotton.

Verticillium wilt caused by soil borne fungus Verticillium dahliae could significantly reduce cotton yield. The Ve1 homologous gene Gbvdr3 is resistant to Verticillium wilt. In order to understand of the function of the promoter Gbvdr3 in Gossypium barbadense, the promoter region of the receptor-like gene Gbvdr3 was obtained by genome walking, and the cis-element in the promoter was identified using the PLACE software in this study. The sequence analysis showed that the promoter contained elements related to stress resistance and light regulation. The cloned promoter was fused to the GUS reporter gene and transformed into Arabidopsis. GUS expression was specifically detected in roots, flowers, and seeds, suggesting that the expression of Gbvdr3 is tissue-specific. Separation and characterization analysis of the promoter of Gbvdr3 provides a platform for further research and application of this gene. Thorough understanding of the function of the Gbvdr3 promoter is important for better understanding of Gbvdr3 function. These results indicated that the promoter of Gbvdr3 was a tissue-specific promoter.

Optimization of pyrethroid and repellent on fabrics against Stegomyia albopicta (=Aedes albopictus) using a microencapsulation technique.

A new approach employing a combination of pyrethroid and repellent is proposed to improve the protective efficacy of conventional pyrethroid-treated fabrics against mosquito vectors. In this context, the insecticidal and repellent efficacies of commonly used pyrethroids and repellents were evaluated by cone tests and arm-in-cage tests against Stegomyia albopicta (=Aedes albopictus) (Diptera: Culicidae). At concentrations of LD50 (estimated for pyrethroid) or ED50 (estimated for repellent), respectively, the knock-down effects of the pyrethroids or repellents were further compared. The results obtained indicated that deltamethrin and DEET were relatively more effective and thus these were selected for further study. Synergistic interaction was observed between deltamethrin and DEET at the ratios of 5 : 1, 2 : 1, 1 : 1 and 1 : 2 (but not 1 : 5). An optimal mixing ratio of 7 : 5 was then microencapsulated and adhered to fabrics using a fixing agent. Fabrics impregnated by microencapsulated mixtures gained extended washing durability compared with those treated with a conventional dipping method. Results indicated that this approach represents a promising method for the future impregnation of bednet, curtain and combat uniform materials.

Influence of hepatic ischemia-reperfusion on postoperative spatial cognitive function in mice.

The aim of this study was to investigate the effects of partial hepatic ischemia/reperfusion (I/R) on postoperative cognitive function in mice. One hundred Kunming mice were randomized into control group (N = 20), sham group (N = 20) and I/R group (N = 60), which was equally divided into 3 subgroups according to the ischemia time (20, 30 and 40 min). Half of the mice in each group underwent a passive avoidance test on the 4th day, and the other underwent the test on the 18th day, which lasted for 6 days before euthanasia for analysis of brain pathology and immunohistochemistry for ChAT. The passive avoidance test showed that there was no significance in the incubation period and number of errors between the control and sham group, but there was a longer incubation period and more errors in the I/R group than control group; at G2, there was no significance between all groups. Hematoxylin-eosin staining of the hippocampus showed that at G1, there was no obvious change in hippocampal neurons in structure and arrangement except for IR/40 min; at G2, there was no significance between all groups. Immunohistochemistry of hippocampus for ChAT showed the following: at G1, there was no significance in average optical density of CA3 area between control and sham group, but optical density was significantly lower in I/R groups with I/R 40 min showing the lowest; at G2, there was no significance between all groups. Pentobarbital has no effect on cognitive function, but hepatic partial ischemia and reperfusion injury does and could become worse over time.

Dietary glutamine supplementation improves growth performance, meat quality and colour stability of broilers under heat stress.

1. The present study was conducted to investigate the effects of dietary glutamine (Gln) supplementation on growth performance, carcase characteristics and meat quality in broilers exposed to high ambient temperature. 2. A total of 240 35-d-old male Arbor Acres broilers were randomly assigned to 4 treatment groups (three replicates of 20 birds per cage). The broilers were kept in a temperature-controlled room at either 23 degrees C (no-stress groups, NS) or 28 degrees C (heat stress groups, HS). The broilers were fed either on a basal diet (control, NS) or on the basal diet supplemented with 0, 0.5 or 1.0% Gln (HS). 3. Compared with the NS, the HS (0% Gln) group gained less weight and consumed less feed, had lower final body weight, gain-to-feed ratio, and abdominal fat yield. Breast meat in HS (0% Gln) had lower pH, water-holding capacity (WHC), a* value, ether extract (EE) content and crude protein (CP) content, and had higher shear force (SF) and L* value. 4. Linear increase were found in groups supplemented with Gln (0, 0.5% and 1.0%) for final body weight, weight gain, feed consumption, gain-to-feed ratio and abdominal fat yield. Supplementation with Gln improved breast meat pH, WHC, SF, L* value, a* value, EE content and CP content in broilers exposed to heat stress. No significant difference was observed in all the indices determined between the HS (1% Gln) and the NS. 5. Heat stress caused obvious breast meat discoloration in L*, a* and b* values. However, dietary supplementation with Gln gave a better colour stability. 6. The results indicated that dietary supplementation with Gln may alleviate heat stress-caused deterioration in growth performance, carcase characteristics, meat quality and meat colour stability of broilers.

Evolution of myrmecophytism in western Malesian Macaranga (Euphorbiaceae).

Plants inhabited by ants (myrmecophytes) have evolved in a diversity of tropical plant lineages. Macaranga includes approximately 300 paleotropical tree species; in western Malesia there are 26 myrmecophytic species that vary in morphological specializations for ant association. The origin and diversification of myrmecophytism in Macaranga was investigated using phylogenetic analyses of morphological and nuclear ITS DNA characters and studies of character evolution. Despite low ITS variation, the combined analysis resulted in a well-supported hypothesis of relationships. Mapping myrmecophytism on all most parsimonious trees resulting from the combined analysis indicated that the trait evolved independently between two and four times and was lost between one and three times (five changes). This hypothesis was robust when tested against trees constrained to have three or fewer evolutionary transformations, although increased taxon sampling for the ITS analysis is required to confirm this. Mapping morphological traits on the phylogeny indicated that myrmecophytism was not homologous among lineages; each independent origin involved a suite of different specializations for ant-plant association. There was no evidence that myrmecophytic traits underwent sequential change through evolution; self-hollowing domatia evolved independently from ant-excavated domatia, and different food-body production types evolved in different lineages. The multiple origins of myrmecophytism in Macaranga were restricted to one small, exclusively western Malesian lineage of an otherwise large and nonmyrmecophytic genus. Although the evolution of aggregated food-body production and the formation of domatia coincided with the evolution of myrmecophytism in all cases, several morphological, ecological, and biogeographic factors appear to have facilitated and constrained this radiation of ant-plants.

Domain structure and mutational analysis of T4 polynucleotide kinase.

T4 polynucleotide kinase (Pnk) is the founding member of a family of 5'-kinase/3'-phosphatase enzymes that heal broken termini in RNA or DNA by converting 3'-PO(4)/5'-OH ends into 3'-OH/5'-PO(4) ends, which are then suitable for sealing by RNA or DNA ligases. Here we employed site-directed mutagenesis and biochemical methods to dissect the domain structure of the homotetrameric T4 Pnk protein and to localize essential constituents of the apparently separate active sites for the 5'-kinase and 3'-phosphatase activities. We characterized deletion mutants Pnk(42-301) and Pnk(1-181), which correspond to domains defined by proteolysis with chymotrypsin. Pnk(1-181) is a monomer with no 3'-phosphatase and low residual 5'-kinase activity. Pnk(42-301) is a dimer with no 5'-kinase and low residual 3'-phosphatase activity. Four classes of missense mutational effects were observed. (i) Mutations K15A, S16A, and D35A inactivated the 5'-kinase but did not affect the 3'-phosphatase or the tetrameric quaternary structure of T4 Pnk. 5'-kinase activity was ablated by the conservative mutations K15R, K15Q, and D35N; however, kinase activity was restored by the S16T change. (ii) Mutation D167A inactivated the 3'-phosphatase without affecting the 5'-kinase or tetramerization. (iii) Mutation D85A caused a severe decrement in 5'-kinase activity and only a modest effect on the 3'-phosphatase; the nearby N87A mutation resulted in a significantly reduced 3'-phosphatase activity and slightly reduced 5'-kinase activity. D85A and N87A both affected the quaternary structure, resulting in a mixed population of tetramer and dimer species. (iv) Alanine mutations at 11 other conserved positions had no significant effect on either 5'-kinase or 3'-phosphatase activity.

The clinical use of small-dose tetracaine spinal anesthesia for transurethral prostatectomy.

UNLABELLED: In a double-blinded study, we compared conventional dose tetracaine (8 mg), small-dose tetracaine (4 mg) with added fentanyl and epinephrine, and small-dose tetracaine (4 mg) with added fentanyl subarachnoid anesthesia. Forty-five patients scheduled for transurethral resection of prostate (TURP) under subarachnoid anesthesia were randomly assigned to Group 1 (8 mg hyperbaric tetracaine), Group 2 (4 mg hyperbaric tetracaine, 10 microg fen-tanyl, and 0.2 mg epinephrine), and Group 3 (4 mg hyperbaric tetracaine, 10 microg fentanyl, and 0.2 mL saline). Evaluations were performed after spinal anesthesia. Subarachnoid block was successful in all patients except one in Group 1, who required general anesthesia by mask. The median peak sensory levels 10 min after the induction of spinal anesthesia in Group 1 was T8, which was significantly higher than Group 2 and Group 3 (P < 0.05). The time of sensory and motor recovery in Group 3 was less than in Groups 1 and 2 (P < 0.05). Hypotension was observed in four patients in Group 1 and none in Groups 2 and 3. We conclude that small-dose 4-mg hyperbaric tetracaine plus 10 microg fentanyl might provide adequate anesthesia and fewer side effects for TURP when compared with the conventional (8 mg) dose. IMPLICATIONS: Small-dose hyperbaric tetracaine (4 mg with 10 microg fentanyl added) may provide adequate anesthesia and fewer side effects for transurethral resection of the prostate.

Axillary brachial plexus block with patient controlled analgesia for complex regional pain syndrome type I: a case report.

BACKGROUND AND OBJECTIVES: Brachial plexus block (BPB) has been cited as a treatment modality for complex regional pain syndrome type I (CRPS I) of the upper limb. However, there are no reports using axillary BPB with patient controlled analgesia (PCA) for the treatment of CRPS I. This report is based on the retrospective observations of the outcome and effects of axillary BPB with PCA in a patient with CRPS I. CASE REPORT: A 32-year-old man suffered from CRPS I of the right upper limb after surgical release of carpal tunnel syndrome of the right hand. Symptoms and signs over the right hand were alleviated under rehabilitation and conventional pharmacological management, but severe painful swelling of the right wrist persisted. Axillary BPB with PCA was performed on the 32nd postoperative day, which soon resulted in significant reduction of pain with gradual improvement of function of the right wrist. CONCLUSIONS: Axillary BPB with PCA may provide patients with CRPS I of the upper limb a feasible and effective treatment. .

Home-based patient-controlled epidural analgesia with bupivacaine for patients with intractable herpetic neuralgia.

This clinical report is based on retrospective observation of the outcome and effects of patient-controlled epidural analgesia (PCEA) with bupivacaine infusion administered at home to five patients with intractable herpetic neuralgia. All patients had severe pain (9 or 10 visual analogue scale [VAS]points) confined to the affected dermatomes, which was refractory to medication. The interval between zoster onset and PCEA application ranged from 27 to 60 days (mean, 37.2 d). The average daily amount of bupivacaine used was 36.5 to 91.2 mg (mean +/- standard deviation, 62.4 +/- 19.7 mg). The duration of PCEA therapy ranged from 10 to 28 days (18.4 +/- 7.6 d). One patient developed drug tolerance. All treatments resulted in effective and satisfactory pain relief (VAS, 0-3), with increase in physical activities to normal levels and easing of sleep and appetite impairment. No deleterious effects were found during PCEA therapy. After discontinuation of PCEA, two patients did not complain of pain but still had slight paresthesia, one of them required low-dose antidepressant for 17 days; three patients continued to have occasional sharp pain (VAS, 2-3) and required low-dose antidepressant and analgesic as-needed for one to six months. These results suggest that PCEA with bupivacaine infusion provides effective pain relief in patients with intractable herpetic neuralgia and is a feasible and effective home treatment modality with limited side effects.

[Surgical treatment for the recurrent patients after palatopharyngoplasty].

OBJECTIVE: To study the surgical treatment for the recurrent patients after palatopharyngoplasty (PPP). METHOD: Five patients which were confirmed recurrence by sleep survey and examinations were reported. RESULT: The pharyngeal cavity was narrower obviously ten months after ppp than before ppp. The anteroposterior and transverse distances were (4.06 +/- 2.94) mm and (11.40 +/- 4.16) mm respectively. After dilatation, the distances were (11.90 +/- 3.25) mm and (21.00 +/- 4.18) mm separately, and were increased significantly than before (P < 0.01). Two patients were cured and three cases marked, and all patients were not recurrent post-operation with no complications. CONCLUSION: The recurrence was mainly concerned with the unsuitable manipulation in PPP. Selecting the cooperation and proper surgical treatment, the better effect was also obtained for the recurrent patients.

Structure and mechanism of yeast RNA triphosphatase: an essential component of the mRNA capping apparatus.

RNA triphosphatase is an essential mRNA processing enzyme that catalyzes the first step in cap formation. The 2.05 A crystal structure of yeast RNA triphosphatase Cet1p reveals a novel active site fold whereby an eight-stranded beta barrel forms a topologically closed triphosphate tunnel. Interactions of a sulfate in the center of the tunnel with a divalent cation and basic amino acids projecting into the tunnel suggest a catalytic mechanism that is supported by mutational data. Discrete surface domains mediate Cet1p homodimerization and Cet1p binding to the guanylyltransferase component of the capping apparatus. The structure and mechanism of fungal RNA triphosphatases are completely different from those of mammalian mRNA capping enzymes. Hence, RNA triphosphatase presents an ideal target for structure-based antifungal drug discovery.

The dose effect of propofol on cerebrovascular reactivity to carbon dioxide in rabbits.

BACKGROUND: Propofol has several properties beneficial to intracranial operation such as reduction in cerebral metabolic rate and cerebral blood flow (CBF) in a dose-dependent manner while leaving autoregulation intact. Several studies have demonstrated that the responsiveness of CBF to changes in arterial carbon dioxide tension (PaCO2) is maintained during propofol anesthesia in both humans and animals. These studies showed a significant difference in the CBF-CO2 reactivity slope between awake and propofol anaesthetized groups, but no comparison with different doses of propofol was made. To determine the dose effect of propofol on cerebrovascular CO2 reactivity, we used laser Doppler flowmetry (LDF) to detect the changes of CBF during propofol anesthesia. METHODS: Ten rabbits were studied using LDF on the parietal cortex. After surgical preparation, anesthesia was maintained with 66% N2O in O2, morphine 10 mg/kg and pancuronium. Three experimental conditions were studied sequentially with intravenous administration of the following drugs: (1) normal saline (control), (2) propofol 20 mg/kg/h i.v., (3) propofol 40 mg/kg/h i.v. Mean arterial pressure, rectal temperature and hematocrit were kept constant. The arterial carbon dioxide tension (PaCO2) was adjusted to three levels during each condition: 20-25 mmHg (hypocapnia), 35-40 mmHg (normocapnia) and 45-50 mmHg (hypercapnia). CBF was measured continuously and recorded after the target PaCO2 had been reached. RESULTS: There were no differences among all conditions in mean arterial pressure and heart rate. The changes of CBF as PaCO2 increased at the three different CO2 levels during each of the conditions were significantly different. The slope of CBF-CO2 reactivity among three different propofol doses was not significantly different. CONCLUSIONS: These data indicate that cerebral vasomotor responsiveness to CO2 during propofol anesthesia is preserved and that the slope of CBF-CO2 reactivity is independent of propofol doses as mean arterial blood pressure is maintained.